Genetic sequencing efforts, such as the Human Genome project, have produced vast amounts of information for basic genetic research that have proven useful in developing advances in health care and drug research. These advances are possible because of improvements in engineering and instrumentation that provide advanced tools for the biotechnology community to continue with basic genetic research. With these advances, scientists can move from basic genomic discoveries to associating specific phenotypes and diseases, and can thereby better identify targets for drug development.
Nucleic acid sequencing and diagnostic methods often analyze samples deposited onto target locations on substrate arrays, including arrays and microarrays, such as microplates, silicon chips and other such supports that retain molecules, such as biological molecules, or biological particles or samples at discrete loci. Microarrays have been used to execute tests on large batches of genetic samples to generate phenotype associations and improve interpretation of the large data sets that result from such tests. A typical microarray, often referred to as a chip, includes a substrate, such as a silicon or silicon-coated substrate, on which a large number of reactive points receive samples for testing. Microarray chips provide a technology that permits operators to increase sample throughput, allowing the screening of large numbers of samples and reducing reagent costs by using submicroliter sample volumes. Preparation of such arrays employs a variety of methodologies, including printed arrays and spotted arrays, with a wide variety of substrate surfaces and different modes of quantification. The resulting microarrays are used as substrates for a variety of biochemical applications.
Some mass spectrometry formats, such as MALDI-TOF formats (e.g., axial MALDI-TOF), combine the sample to be tested with a matrix material, such as an organic acid, onto a substrate. When dried, the material forms a crystal structure. During MALDI-TOF mass spectrometry molecules are ionized from different spots of the crystal surface and travel to a particle detector, where the time-of-flight traveled indicates the mass of the particle. With some substrates, when the biomolecular sample and the porous matrix material required for mass spectrometry are loaded onto the substrate, the upper surface of the resulting crystal structures that form have been found to be rounded and to vary significantly in height (z-axis) within the same target sample loci. Because the height of the sample-matrix crystal structure can vary significantly in the z-direction, the distances traveled to the particle detector of ionized particles also can vary significantly within the same sample. A higher degree of variability for the travel distance of the same size particles from the same target loci on a substrate, results in a lower level of resolution for the mass spectra obtained by MALDI-TOF mass spectrometry analysis. Higher levels of mass spectra resolution are useful in combination with high throughput capability of the MALDI-TOF methods.